TGF-β1 as a prognostic factor in the process of early osteoarthrosis in the rabbit knee

AbstractObjective To assess changes in knee joint fluid concentrations of transforming growth factor-β1 (TGF-β1) and proteoglycan (PG) fragments during the early course of post-traumatic osteoarthrosis (OA) after meniscectomy in the rabbit knee, and to ascertain whether the concentrations of these substances shortly after operation could be used as prognostic markers for the OA process.Design In 15 rabbits with medial meniscectomy in one knee and a sham operation in the other knee, synovial lavage fluid samples were taken repeatedly, before operation, every third week post-operatively until 12 weeks, thereafter every sixth week, and at death. Five rabbits each were killed at 13, 25 and 40 weeks. Synovial lavage fluid samples from five non-operated rabbits served as controls. At death, two histological scores were formed that characterized the highest (MAX) and the overall (ALL) degree of OA changes in each joint.Results TGF-β1 and PG fragment concentrations in synovial lavage fluid correlated highly (R=0.81, P< 0.001). Both OA scores were higher in meniscectomized than controls (P< 0.05). The synovial lavage fluid concentration of TGF-β1 at 3 weeks, but no other time point, correlated to the histological scores (ALL, R=0.58; MAX, R=0.52;P< 0.001).Conclusion Higher concentrations of TGF-β1 in synovial lavage fluid early after surgery seemed indicative for the later development of more severe OA changes in contrast to lower concentrations. The association between TGF-β1 and the changes found later in the cartilage was underlined by the high correlations between this substance and PG fragment concentrations in synovial lavage fluid at all time points

Simultaneous changes in bone mineral density and articular cartilage in a rabbit meniscectomy model of knee osteoarthrosis

AbstractObjective It was hypothesized that increased bone mineral density of the medial proximal tibia would precede or coincide with the development of more severe cartilage changes after meniscectomy.Methods In a rabbit knee model, mineral density of subchondral bone and changes of articular cartilage were monitored 13 to 40 weeks after medial meniscectomy or a sham operation.Results Both procedures resulted in a decrease of bone mineral density, especially of the medial proximal tibia, which persisted up to 40 weeks (P< 0.02–0.0007). Meniscectomy induced cartilage changes typical for osteoarthrosis (P< 0.009), which progressed over time on the posterior aspect of the medial tibial plateau (P< 0.009), which is physiologically covered by the meniscus, but the procedure also induced iatrogenic changes which were located mainly on the anterior aspect of the concerned compartment, and which did not progress or develop to osteoarthrosis.Conclusions The data suggest that the cartilage changes after meniscectomy in this animal model are caused by the surgical trauma, subsequent limb misuse, and altered load distribution, and initially associated by a decrease not an increase in bone mineral density of the proximal tibia. Moreover, the cartilage changes progressed without a simultaneous increase of the bone mineral density at corresponding sites

Polycyclic aromatic hydrocarbons (PAHs) degradation by laccase from a tropical white rot fungus Ganoderma lucidum

Laccase enzyme was produced from an isolate of the white rot fungus, Ganoderma lucidum Chaaim-001 BCU. The enzyme was subsequently evaluated for its degradative ability towards sixteen types of polycyclic aromatic hydrocarbons (PAHs). The G. lucidum laccase degraded antracene completely with or without a redox mediator (2 mM 1-hydroxybenzotriazole) and also degraded benzo[a]pyrene, fluorine, acenapthene, acenaphthylene and benzo[a]anthracene up to 100.0, 98.6, 95.4, 90.1 and 85.3 %,respectively, when the mediator was present. In the absence of the mediator, the ability to degrade these compounds dropped to 71.71, 62.9, 80.49, 85.85 and 9.14% respectively. Compared to the laccase enzyme from Trametes vesicolor, G. lucidum laccase appeared to retain more of its capability todegrade these PAHs when the mediator was absent

Nonlinear elasticity of stiff biopolymers connected by flexible linkers

Networks of the biopolymer actin, cross-linked by the compliant protein filamin, form soft gels. They can, however, withstand large shear stresses due to their pronounced nonlinear elastic behavior. The nonlinear elasticity can be controlled by varying the number of cross-links per actin filament. We propose and test a model of rigid filaments decorated by multiple flexible linkers that is in quantitative agreement with experiment. This allows us to estimate loads on individual cross-links, which we find to be less than 10 pN. © 2009 The American Physical Society

Not ‘Islands, Entire of Themselves’: Exploring the Spatial Context of City-level Robbery Rates

The current study examines spatial dependence in robbery rates for a sample of 1,056 cities with 25,000 or more residents over the 2000–2003 period. Although commonly considered in some macro-level research, spatial processes have not been examined in relation to city-level variation in robbery. The results of our regression analyses suggest that city robbery rates are not spatially independent. We find that spatial dependence is better accounted for by spatial error models than by spatial lag models. Further exploration of various spatial weights matrices indicates that robbery rates of cities within the same state are related to robbery rates of other cities within the same state, regardless of their proximity. Our analyses illustrate how systematic inquiry into spatial processes can alert researchers to important omitted variable biases and identify intriguing problems for future research

TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells

Upon activation by antigen, B cells form germinal centers where they clonally expand and introduce affinity-enhancing mutations into their B cell receptor genes. Somatic mutagenesis and class switch recombination in germinal center B cells are initiated by the activation-induced cytidine deaminase (AID). Upon germinal center exit, B cells differentiate into antibody-secreting plasma cells. Germinal center maintenance and terminal fate choice require transcriptional reprogramming that associates with a substantial reconfiguration of DNA methylation patterns. Here we examine the role of TET proteins, enzymes that facilitate DNA demethylation and promote a permissive chromatin state by oxidizing 5-methylcytosine, in antibody-mediated immunity. Using a conditional gene ablation strategy, we show that TET2 and TET3 guide the transition of germinal center B cells to antibody-secreting plasma cells. Optimal AID expression requires TET function, and TET2 and TET3 double-deficient germinal center B cells show defects in class switch recombination. However, TET2/TET3 double-deficiency does not prevent the generation and selection of high-affinity germinal center B cells. Rather, combined TET2 and TET3 loss-of-function in germinal center B cells favors C-to-T and G-to-A transition mutagenesis, a finding that may be of significance for understanding the etiology of B cell lymphomas evolving in conditions of reduced TET function

Space power distribution system technology. Volume 2: Autonomous power management

Electrical power subsystem requirements, power management system functional requirements, algorithms, power management subsystem, hardware development, and trade studies and analyses are discussed

'It's a Form of Freedom': The experiences of people with disabilities within equestrian sport

This paper explores the embodied, gendered experiences of disabled horse‐riders. Drawing on data from five in‐depth interviews with paradressage riders, the ways in which their involvement in elite disability sport impacts upon their sense of identity and confidence are explored, as well as the considerable health and social benefits that this involvement brings. Social models of disability are employed and the shortcomings of such models, when applied to disability sport, are highlighted. The data presented here demonstrates the necessity of seeing disability sport as an embodied experience and acknowledging the importance of impairment to the experiences of disabled athletes. Living within an impaired body is also a gendered experience and the implications of this when applied to elite disability sport are considered